Technical Field
This invention generally pertains to devices, apparatus, and methods for separation of serum from whole blood and potentiation of agglutination reactions in microfluidic devices. Agglutination reactions involving antigen:antibody reactions are useful in cross-matching for blood transfusion.
Description of the Related Art
Analysis of blood prior to transfusion or for clinical assessments relies on diagnostic devices, such as cross-matching or blood-typing devices, and blood chemistry monitors that measure metabolites such as glucose or cholesterol. Such devices must frequently use serum, the uncolored fluid portion of the blood containing analytes of interest to clinicians. Serum samples are separated from whole blood before analysis to remove red blood cells and clotting factors, which have the potential to interfere with cross-match agglutination reactions, colorimetric tests, as well as contribute to hematocrit-dependent variations amongst samples. Therefore, prior to testing, a preprocessing operation is required in which the blood sample is separated into a serum and a clot containing red blood cells.
In the conventional method of serum separation, a whole blood sample is placed in a blood collection tube, allowed to clot, and subjected to centrifugal separation, which enables collection of the serum fraction. However, there has been a dramatic transition in diagnostic analysis from the macroscale to the microscale, with specimen volume requirements decreasing from milliliters to microliters, thereby reducing assay times from hours to minutes. The conventional method of serum separation, requiring sample centrifugation, is obviously not amenable to microscale adaptation. As the engineering of microfluidic diagnostic devices continues to be the focus of competitive research, there is a neglected need for improvements in the preparation of samples for analysis. In adapting these devices for clinical diagnosis, special features are needed to provide serum separated from red blood cells and clotting factors.
Administration of blood in the form of packed erythrocytes or whole blood is often critical in the treatment of trauma, hypovolemic shock, anemia and clotting disorders. Blood transfusion typically requires characterization of the donor blood so as to match the ABO blood type of the donor and recipient, or, more generally, requires a cross-match analysis. This is done to avoid a hemolytic transfusion reaction in which red cells having a major incompatibility antigen are inadvertently administered to a recipient having an antibody to that antigen, and also to avoid the minor side reaction in which a red cell antigen in the recipient's blood is attacked by antibodies in the plasma of the donor. Serious consequences such as kidney failure or splenic rupture can result from a transfusion of mismatched blood.
Currently, medical technicians in the field do not have access to a simple and accurate means of evaluating a donor and recipient pair for possible transfusion reactions during emergency medical treatment, for example, during military operations. Tube agglutination assays are currently used prior to blood transfusion, however these assays are cumbersome and involve erythrocyte preparation and long incubation times. These assays may not always lead to consistent results depending upon the experience of the technician. Additionally, some technicians do not have access to a laboratory qualified to perform agglutination assays. Therefore, there is a strong need in the art for a blood cross-matching device that is quick and simple to use and thus amenable for evaluation of donor and recipient transfusion compatibility during emergency medical care. The present invention fulfills these needs and provides further related advantages.